Bee venom melittin blocks neutrophil O2 ? production

Abstract

Bee venom (BV) is used in folk medicine to treat arthritis. It has antiinflammatory effects in animal models of rheumatic disease. We have studied the effects of BV on human neutrophil production of superoxide (O2-) and hydrogen peroxide, finding potent, nontoxic, dose-dependent production inhibition. Melittin, the major fraction of BV (50-70%) shows high-affinity calmodulin binding (Kd 3 nM). Drugs which bind calmodulin, such as trifluoperazine, inhibit O2- production by human neutrophils. For these reasons we have investigated the effect of melittin and other BV peptides on O2- production by human peripheral blood leukocytes. We show that melittin inhibited O2- production both pre- and poststimulation in contrast to other BV fractions which were without effect. Oxygen radicals and their derivatives from inflammatory cells are implicated in the tissue damage occurring during inflammation. The inhibition is due to a direct effect on cells, and not indicator medium, dismutation, toxic or scavenging effects. We propose that melittin may serve as a prototype small (mol wt 1280), cationic, amphipathic, calmodulin-binding, membrane-active, superoxide-production-inhibiting peptide, providing a model for peptides which could have a role in in vivo regulation of radical production.

Effects of bee venom on the pro-inflammatory responses in RAW264.7 macrophage cell line

“…However, the major anti-inflammatory molecule has not yet been elucidated. In addition, our results could not rule out a potential scavenger activity of some of the BV compounds, although it has been reported that whole BV and mellitin by inhibiting superoxide production have anti-inflammatory effects that are not due to toxic or scavenging effects (Somerfield et al, 1984(Somerfield et al, , 1986. Therefore, further studies are needed to identify the major components of BV that are responsible for the antiinflammatory effects.…”

“…Non-peptide components consist of histamine, dopamine and noradrenaline (Habermann, 1971;Banks and Shipolini, 1986;Lee et al, 2001). Each BV substance has been the subject of many studies employing diverse methodologies in an effort to prove their anti-inflammatory effect (Martin and Hartter, 1980;Koburova et al, 1985;Somerfield et al, 1986;Saini et al, 1997). However, the major anti-inflammatory molecule has not yet been elucidated.…”

Bee Venom Pretreatment Has Both an Antinociceptive and Anti-Inflammatory Effect on Carrageenan-Induced Inflammation.

“…In addition to an effect on PLA 2 , melittin has been reported to block neutrophil superoxide production [36]. In particular, it has been shown that human leukemic cells treated with sublytic doses of melittin become resistant to complement-mediated lysis [32].…”

Apitoxin protects rat pups brain from propionic acid-induced oxidative stress: The expression pattern of Bcl-2 and Caspase-3 apoptotic genes

“…First, the 457 BV major constituent melittin and phospholipase (PLA2) have been 458 proved to have the ability to scavenge nitric oxide (NO) and ROS 459 (Cernanec et al, 2002;Park et al, 2007). Secondly, melittin was 460 found to potently inhibit the human peripheral-blood leukocytic 461 production of superoxide (O 2 À ) and hydrogen peroxide in a 462 nontoxic and dose-dependent manner, as melittin may serve as a 463 prototypic small, cationic, amphipathic, membrane-active, super-464 oxide-production-inhibiting, peptide to provide a model peptide 465 that may play a role in the in vivo regulation of radical production 466 (Somerfield et al, 1986). Third, it was also found that BV has an 467 inhibitory effect on the LPS-induced generation of ROS and the 468 release of calcium.…”